Discovery: Model Generation and Validation

ASC offers a full suite of comprehensive services tailored towards your preclinical-stage cell and gene therapy (CGT) projects. Leverage our fully integrated service platform starting with in vitro model generation and cell-based assays, followed by custom animal models and in vivo assays for target validation for early go-no-go decisions of your biotherapeutics. We have a unique team of scientists with multidisciplinary expertise in CRISPR/ genome engineering technologies, stem cell biology, immuno-oncology, gene therapy models, and viral vectors to plan and execute every aspect of your CGT projects. We can generate in vitro and in vivo models, design viral vectors (AAV, lentivirus) and develop proof-of-concept and target validation assays specific to your therapeutic pipeline needs.

Discovery: Preclinical Cell & Gene Therapy Services Categories

Cell Line
Model Generation

Custom stable cell line model generation to generate biorelevant disease models to validate your cell and gene therapy candidates.

Cell Line
Model Generation

Mouse Model

Precision genome engineering to generate mouse/rat models of human diseases including humanized mouse models for CGT projects.

Mouse Model

Cell Line Model Validation

Fully customizable assay development for phenotypic characterization and validation of your engineered cell line models.

Cell Line Model Validation

In VivoAnimal Model Validation

ASC offers fully customizable assays for phenotypic characterization and validation of your genetically engineered animal models.

Animal Model Validation

Application Notes

Generating FVIII Knockout (KO) Mouse Model For Testing and Screening for Hemophilia A Gene Therapy and Other Therapeutic Candidates

Applied StemCell has generated a FVIII Knockout (KO) mouse model to validate the efficacy and potency of an in vivo genome editing-based approach to treat Hemophilia A, a monogenic disease caused by a mutation in the factor VIII (F8) gene resulting in a deficiency of the blood clotting factor VIII (FVIII). This KO mouse provides an efficient in vivo model for testing your gene therapy constructs, as well as for safety and toxicity screening.

Read our paper detailing the model generation, potency assay development and optimizing strategies for gene therapy constructs.


Technical Details

Cell and Gene Therapy has progressed very rapidly with the advent of new technologies for genome editing, stem cell and immuno-oncology applications. Applied StemCell (ASC) has been at the forefront of these technologies for >12 years and has been a leading CRO service provider for discovery phase of our customer’s cellular and gene therapy projects. Using CRISPR/cas9 and our proprietary TARGATT™ transgene integration technologies, we have generated 1300+ custom cell line and animal models for target discovery, disease modeling and drug screening applications.

We now leverage our extensive experience in cell and animal biology to develop clinically relevant in vitro and in vivo models and downstream validation of these models for more advanced cellular and gene therapy pipelines.

Cell and gene therapy drugs have a unique mechanism of action. Unlike traditional small molecule drugs, detailed characterization of CGT involves development of custom assays specific to the unique mechanism of action of the drug. Due to target specificity of these drugs, traditional animal/ cell line models may not work. ASC specializes in developing the ideal research model for your biotherapeutic that would enable you to have better translation of your results in clinical setting.

Have an idea but need the resources to develop your cell and gene therapy product? We can help!

  • Derive/ differentiate stem cell lines
  • Genetically engineer cell lines for immunotherapy applications, cellular therapy
  • Design and generate gene therapy constructs
  • Screen for tissue-specific promoters
  • Viral vector serotypes analysis (for AAV and lentiviral)-based delivery of gene therapy products,
  • Characterize the mechanism of action of your drug candidate.

We also provide expert consultation and downstream assay development and IND-enabling studies to advance your biotherapeutic projects.


Cell and Gene Therapy Applications:

  • Chen, H., Shi, M., Gilam, A., Zheng, Q., Zhang, Y., Afrikanova, I., ... & Chen-Tsai, R. Y. (2019). Hemophilia A ameliorated in mice by CRISPR-based in vivo genome editing of human Factor VIII. Scientific reports9(1), 1-15.

Other CRO Services:

  • Mace, E. M., Paust, S., Conte, M. I., Baxley, R. M., Schmit, M., Mukherjee, M., ... & Akdemir, Z. C. (2019). Human NK cell deficiency as a result of biallelic mutations in MCM10. bioRxiv, 825554.
  • Baskfield, A., Li, R., Beers, J., Zou, J., Liu, C., & Zheng, W. (2019). Generation of an induced pluripotent stem cell line (TRNDi004-I) from a Niemann-Pick disease type B patient carrying a heterozygous mutation of p. L43_A44delLA in the SMPD1 gene. Stem cell research37, 101436.
  • Hong, J., Xu, M., Li, R., Cheng, Y. S., Kouznetsova, J., Beers, J., ... & Zheng, W. (2019). Generation of an induced pluripotent stem cell line (TRNDi008-A) from a Hunter syndrome patient carrying a hemizygous 208insC mutation in the IDS gene. Stem cell research37, 101451.
  • Cheng, Y. S., Li, R., Baskfield, A., Beers, J., Zou, J., Liu, C., & Zheng, W. (2019). A human induced pluripotent stem cell line (TRNDi007-B) from an infantile onset Pompe patient carrying p. R854X mutation in the GAA gene. Stem cell research37, 101435.
  • Yang, S., Cheng, Y. S., Li, R., Pradhan, M., Hong, J., Beers, J., ... & Zheng, W. (2019). An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p. R401X mutation in the NGLY1 gene. Stem cell research39, 101496.
  • Baskfield, A., Li, R., Beers, J., Zou, J., Liu, C., & Zheng, W. (2019). An induced pluripotent stem cell line (TRNDi009-C) from a Niemann-Pick disease type A patient carrying a heterozygous p. L302P (c. 905 T> C) mutation in the SMPD1 gene. Stem cell research38, 101461.
  • Huang, W., Xu, M., Li, R., Baskfield, A., Kouznetsova, J., Beers, J., ... & Zheng, W. (2019). An induced pluripotent stem cell line (TRNDi006-A) from a MPS IIIB patient carrying homozygous mutation of p. Glu153Lys in the NAGLU gene. Stem Cell Research, 101427.
  • Sundararaj, K. P., Rodgers, J., Angel, P., Wolf, B., & Nowling, T. K. (2020). Neuraminidase activity mediates IL-6 production through TLR4 and p38/ERK MAPK signaling in MRL/lpr mesangial cells. bioRxiv.
  • Li, R., Baskfield, A., Lin, Y., Beers, J., Zou, J., Liu, C., ... & Zheng, W. (2019). Generation of an induced pluripotent stem cell line (TRNDi003-A) from a Noonan syndrome with multiple lentigines (NSML) patient carrying a p. Q510P mutation in the PTPN11 gene. Stem cell research34, 101374.
  • Li, R., Pradhan, M., Xu, M., Baskfield, A., Farkhondeh, A., Cheng, Y. S., ... & Rodems, S. (2018). Generation of an induced pluripotent stem cell line (TRNDi002-B) from a patient carrying compound heterozygous p. Q208X and p. G310G mutations in the NGLY1 gene. Stem Cell Research, 101362.
  • Poli, M. C., Ebstein, F., Nicholas, S. K., de Guzman, M. M., Forbes, L. R., Chinn, I. K., ... & Coban-Akdemir, Z. H. (2018). Heterozygous Truncating Variants in POMP Escape Nonsense-Mediated Decay and Cause a Unique Immune Dysregulatory Syndrome. The American Journal of Human Genetics, 102, 1-17

Vozdek, R., Long, Y., & Ma, D. K. (2018). The receptor tyrosine kinase HIR-1 coordinates HIF-independent responses to hypoxia and extracellular matrix injury. Sci. Signal.11(550), eaat0138.

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